Skip to main content
SpringerLink
Log in

An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher’s exact and Hardy–Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p<0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p<0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Batzer MA, Arcot SS, Phinney JW, Alegria-Hartman M, Kass DH, Milligan SM, Kimpton C, Gill P, et al. 1996 Genetic variation of recent Alu insertions in human populations. J. Mol. Evol. 42 22–29

    Article  CAS  PubMed  Google Scholar 

  • Benessiano J, Crestani B, Mestari F, Klouche W, Neukirch F, Hacein-Bey S, Durand G and Aubier M 1997 High frequency of a deletion polymorphism of the angiotensin-converting enzyme gene in asthma. J. Allergy Clin. Immunol. 99 53–57

    CAS  PubMed  Google Scholar 

  • Bland JM and Altman DG 2000 Statistics notes: the odds ratio. Br. Med. J. 320-1468

  • Ehlers MR and Riordan JF 1989 Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry 28 5311–5318

  • Chagani T, Paré PD, Zhu S, Weir TD, Bai TR, Behbehani NA, Fitzgerald JM and Sandford AJ 1999 Prevalence of tumor necrosis factor-alpha and angiotensin converting enzyme polymorphisms in mild/moderate and fatal/near-fatal asthma. Am. J. Respir. Crit. Care Med. 160 278–282

    Article  CAS  PubMed  Google Scholar 

  • Ding QL, Sun SF, Cao C and Deng ZC 2012 Association between angiotensin-converting enzyme I/D polymorphism and asthma risk: a meta-analysis involving 11,897 subjects. J. Asthma. 49 557–562

    Article  CAS  PubMed  Google Scholar 

  • El-Shafei MS, Farres MN and Shahin RY 2012 Evaluation of angiotensin converting enzyme gene polymorphism and susceptibility to bronchial asthma among Egyptians. Allergol. Immunopathol. (Madr.) 40 275–280

  • Eryüksel E, Ceyhan BB, Bircan R, Avşar M and Cirakoğlu B 2009 Angiotensin converting enzyme gene polymorphism in Turkish asthmatic patients. J. Asthma 46 335–338

  • Fuller RW, Dixon CMS, Cuss FMC and Barnes PJ 1987 Bradykinin-induced bronchoconstriction in humans. Mode of action. Am. Rev. Respir. Dis. 135 176–180

    CAS  PubMed  Google Scholar 

  • Gao J, Lin Y, Xiao Y, Xu K, Xu W, Zhu Y, Ma Y and Bai Y 2000 Polymorphism of angiotensin-converting enzyme gene and genetic susceptibility to asthma with familial aggregation. Chin. Med. Sci. J. 15 24–28

    CAS  PubMed  Google Scholar 

  • Holla L, Vasku A, Znojil V, Siskova L and Vacha J 1999 Association of 3 gene polymorphisms with atopic diseases. J. Allergy Clin. Immunol. 103 702–708

    Article  CAS  PubMed  Google Scholar 

  • Ismail M, Akhtar N, Nasir M, Firasat S, Ayub Q and Khaliq S 2004 Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients. J. Biochem. Mol. Biol. 37 552–555

    Article  CAS  PubMed  Google Scholar 

  • Lee YC, Cheon KT, Lee HB, Kim W, Rhee YK and Kim DS 2000 Gene polymorphisms of endothelial nitric oxide synthase and angiotensin-converting enzyme in patients with asthma. Allergy 55 959–963

  • Malerba G and Pignatti PF 2005 A review of asthma genetics: gene expression studies and recent candidates. J. Appl. Genet. 46 93–104

    PubMed  Google Scholar 

  • Martinez FD 2007 Genes, environments, development and asthma: a reappraisal. Eur. Respir. J. 29 179–184

    Article  CAS  PubMed  Google Scholar 

  • Masoli M, Fabian D, Holt S, Beasley R and Global Initiative for Asthma (GINA) Program 2004 The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy 59 469–478

  • Mathew J, Sleight P, Lonn E, Johnstone D, Pogue J, Yi O, et al. 2001 Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation 104 1615–1621

  • Munir S, Rahman SB, Rehman S, Saba N, Naluai ÅT, Agha H, Ahmad W, Mazhar K 2016 The Angiotensin-converting enzyme gene insertion polymorphism: a higher risk for psoriasis in males. Br. J. Dermatol. doi:10.1111/bjd.14653

  • Nakahama H, Obata K, Nakajima T, Nakamura H, Kitada O, Sugita M, Fujita Y, Kawada N, et al. 1999 Renin-angiotensin system component gene polymorphism in Japanese bronchial asthma patients. J. Asthma 36 187–193

  • Ortega VE, Meyers DA and Bleecker ER 2015 Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Pharmgenomics Pers. Med. 8 9–22

    PubMed  PubMed Central  Google Scholar 

  • Pak PRwire on February 21st, 2009. 10-20 pc Pakistani children suffering from Asthma Posted by Dr MosavirAnsarie

  • Panahloo A, Andres C, Mohamed-Ali V, Gould MM, Talmud P, Humphries SE and Yudkin JS 1995 The insertion allele of the ACE gene I/D polymorphism. A candidate gene for insulin resistance? Circulation 92 3390–3393

  • Rehman S, Saba N, Akhtar N, Munir S, Ahmed W and Khanum A 2015 Angiotensin converting enzyme gene I/D polymorphism in Pakistani rheumatic heart disease patients and healthy controls. Int. Cardiovasc. Res. J. 9 169–172

    Google Scholar 

  • Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P and Soubrier F 1990 An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J. Clin. Invest. 86 1343–1346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sambrook J and Russel DW 2001 Molecular cloning: a laboratory manual, vol.1. 6.4 3rd ed. (N.Y: Cold Spring Harbor Laboratory Press)

    Google Scholar 

  • Schremmer DE, Hermann A, Fink E, Fritz H and Roscher AA 1999 Identification and occurrence of mRNAs for components of the kallikrein –kinin system in human skin and in skin diseases. Immunopharmacology 43 287–291

  • Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F and Soubrier F 1992 Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am. J. Hum. Genet. 51 197–205

    CAS  PubMed  PubMed Central  Google Scholar 

  • Urhan M, Degirmenci I, Harmanci E, Gunes HV, Metintas M and Basaran A 2004 High frequency of DD polymorphism of the angiotensin-converting enzyme gene in Turkish asthmatic patients. Allergy Asthma Proc. 25 243–247

    CAS  PubMed  Google Scholar 

  • Wang YK, He HL, Chen XL, Sun CY, Zhang YZ and Zhou BC 2008 Production of novel angiotensin I-converting enzyme inhibitory peptides by fermentation of marine shrimp Aceteschinensis with Lactobacillus fermentum SM 605. Appl. Microbiol. Biotechnol. 79 785–791

    Article  CAS  PubMed  Google Scholar 

  • Yang HY, Erdos EG and Levin Y 1970 A dipeptidylcarboxypeptidase that converts angiotensin I and inactivates bradykinin. Biochim. Biophys. Acta. 214 374–376

    Article  CAS  PubMed  Google Scholar 

  • Yildiz P, Oflaz H, Cine N, Genchallac H, Erginel-Unaltuna N, Yildiz A and Yilmaz V 2004 Endothelial dysfunction in patients with asthma: the role of polymorphisms of ACE and endothelial NOS genes. J. Asthma 41 159–166

  • Zhang YG, Li XB, Zhang J, Huang J, He C, Tian C, Deng Y, Wan H, et al. 2011 The I/D polymorphism of angiotensin-converting enzyme gene and asthma risk: a meta-analysis. Allergy 66 197–205

Download references

Author information

Authors and Affiliations

  1. Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan

    Nusrat Saba, Osman Yusuf, Sadia Rehman, Saeeda Munir, Sheeraz Ahmad, Atika Mansoor & Ghazala K Raja

Authors
  1. Nusrat Saba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osman Yusuf
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sadia Rehman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saeeda Munir
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sheeraz Ahmad
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Atika Mansoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ghazala K Raja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nusrat Saba.

Additional information

Corresponding editor: Sarah H Elsea

[Saba N, Yusuf O, Rehman S, Munir S, Ahmad S, Mansoor A and Raja GK 2016 An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls. J. Biosci.]

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Saba, N., Yusuf, O., Rehman, S. et al. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls. J Biosci 41, 439–444 (2016). https://doi.org/10.1007/s12038-016-9617-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12038-016-9617-x

Keywords

Search

Navigation